In the March issue of The American Journal of Human Genetics, two groups report that mutations in the IKBKAP gene, encoding the protein IKAP, cause Familial Dysautonomia (FD). Two single base pair mutations in this gene account for nearly 100% of FD cases, and this finding will revolutionize genetic testing for this devastating disorder.

FD is almost exclusively found in people of Ashkenazi Jewish origin, and it is estimated that 1 out of every 32 people in this population carry an FD mutation. People with two mutant copies of the IKBKAP gene show poor development of and degeneration of the sensory and autonomic nervous systems. The symptoms in these affected individuals include: abnormal sweating, hypertension, difficulty feeding and sucking, gastrointestinal dysfunction, and insensitivity to pain. FD is fatal; only 50% of patients reach age 30 years.

The major FD mutation, which accounts for 99.5% of disease chromosomes, results in aberrant splicing of the IKBKAP RNA and thus the loss of one of the coding regions for the IKAP protein. A second, much less common mutation was found to cause a single amino acid change in a putative regulatory region of the protein. Together, these mutations are believed to account for all of the Ashkenazi Jewish cases of FD. With this finding, genetic testing for FD will become very effective and much less expensive.

The function of IKAP is not well understood, but the discovery that IKBKAP is involved in FD opens wide the doors for experimentation that will hopefully someday provide a cure.

###

For the full text of these articles, "Tissue-specific expression of a splicing mutation in the IKBKAP gene causes Familial Dysautonomia" by Susan Slaugenhaupt et al. and "Familial Dysautonomia is caused by mutations of the IKAP gene" by Sylvia Anderson et al., please contact The American Journal of Human Genetics at http://www.ajhg.org.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.